Deacetylated I-I2-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading

• Published in: Cellular signalling Vol. 25; no. 2; pp. 539 - 551
• Main Authors: Lee, Mi, Koh, Ara, Park, Dohyun, Jang, Jin-Hyeok, Kwak, Dongoh, Jeon, Hyeona, Kim, Jaeyoon, Choi, Eun-Jeong, Jeong, Heeyoon, Suh, Pann-Ghill, Ryu, Sung
• Format: Journal Article
• Language: English
• Published: 01-02-2013
• Subjects: Affinity; Brain; Cellular; Control; Modulation; Progressions; Regulators; Temporal logic
• ISSN: 0898-6568
• DOI: 10.1016/j.cellsig.2012.11.006

Ras homolog enriched in brain (Rheb) regulates diverse cellular functions by modulating its nucleotide-bound status. Although Rheb contains a high basal GTP level, the regulatory mechanism of Rheb is not well understood. In this study, we propose soluble I-I2-tubulin acts as a constitutively active Rheb activator, which may explain the reason why Rheb has a high basal GTP levels. We found that soluble I-I2-tubulin is a direct Rheb-binding protein and that its deacetylated form has a high binding affinity for Rheb. Modulation of both soluble and acetylated I-I2-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated I-I2-tubulin is increased but that of GTP-bound Rheb is decreased. Constitutively active Rheb-overexpressing cells showed an abnormal mitotic progression, suggesting the deacetylated I-I2-tubulin-mediated regulation of Rheb status may be important for proper mitotic progression. Taken together, we propose that deacetylated soluble I-I2-tubulin is a novel type of positive regulator of Rheb and may play a role as a temporal regulator for Rheb during the cell cycle.